The sulfidopeptide leukotrienes LTC, LTD, and LTE are potent airway contractile agonists and mucus secretagogues derived from arachidonic acid by 5-lipoxygenation and subsequent conjugation of glutathione through a thioether link at C-6 of the eicosanoid backbone. Leukotrien C4 is produced intracellularly and exported from cells. Once exported, the glutamic acid and glycine residues are sequentially cleaved from the molecule to form LTD4 and LTE4, respectively. Although the presence of a specific receptor for LTC4 is controversial, there is general consensus that there is a distinct receptor, termed by this group as LTRd, which recognizes LTD4 and LTE4; evidence presented herein suggests that LTC4 is not an agonist at this receptor. Thus, the removal of the glutamic acid residue from LTC4 by gamma-glutamyl transpeptidase (E.C.2.3.2.2; gamma-GT) may be an important regulatory step in leukotriene bioactivity. Based on this information, they tender the following hypothesis: because only LTC4 is produced and exported by normal cells and because LTRd does not recognize LTC4, bioconversion of leukotriene C4 (LTC4) by gamma-GT to its 6 cysteinyl-glycol analogue, LTD4, represents a critical control step in the expression of the biological activity of the sulfidopeptide leukotrienes. This step may be subject to modulation in the inflammatory microenvironment. This hypothesis will be tested in three specific aims. In the first, the functional expression of gamma-GT will be studied in airway tissues and cells. In the second, pulmonary forms of gamma-GT will be isolated by molecular cloning. In the third, antibodies to pulmonary specific forms gamma-GT (if they exist) will be prepared. Taken together, these experiments will provide information on the tissue expression of gamma-GT and how it is regulated in the inflammatory micro-environment.